Pyrazole[3,4-d]pyrimidine derivatives loaded into halloysite as potential CDK inhibitors

Uncontrolled cell proliferation is a hallmark of cancer as a result of rapid and deregulated progression through the cell cycle. The inhibition of cyclin-dependent kinases (CDKs) activities is a promising therapeutic strategy to block cell cycle of tumor cells. In this work we reported a new example of nanocomposites based on halloysite nanotubes (HNTs)/pyrazolo[3,4-d]pyrimidine derivatives (Si306 and Si113) as anticancer agents and CDK inhibitors. HNTs/Si306 and HNTs/Si113 nanocomposites were synthesized and characterized. The release kinetics were also investigated. Antitumoral activity was evaluated on three cancer cell lines (HeLa, MDA-MB-231 and HCT116) and the effects on cell cycle arrest in HCT116 cells were evaluated. Finally, molecular dynamics simulations were performed of the complexes between Si113 or Si306 and the active site of both CDK 1 and 2.
The work was financially supported by the University of Palermo. The work was carried out in the frame of the PON “AIM: Attrazione e Mobilità Internazionale” No. 1808223 project. SS and GG wish to acknowledge the AIRC project 2019 code 23725. The authors would thank Dr. Susanna Guernelli (University of Bologna) for TEM and SEM measurements.